HUMAN PLACENTAL SYNCYTIOTROPHOBLAST MICROVILLOUS MEMBRANES IMPAIR MATERNAL VASCULAR ENDOTHELIAL FUNCTION

Objective To investigate the hypothesis that, should there be an incre ase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction . Design Syncytiotrophoblast microvillous membrane (STBM) vesicles, pr epared from normal term placentae, were perfused through small subcuta neous arteries isolated from fat biopsies obtained at caesarean sectio n. Endothelial function of these arteries was studied by determining a cetylcholine-induced relaxation after preconstriction with noradrenali ne. As controls, physiological buffer or red blood cell membranes in p hysiological buffer were used and endothelial function similarly estim ated. Transmission electron microscopy was performed on arteries after perfusion. Sample STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrel ated to pre-eclampsia, were suspended in physiological buffer. Subcuta neous fat arteries were obtained from a separate group of 13 normotens ive pregnant women, also undergoing elective caesarean section at term . Results Perfusion with red blood cell membranes or physiological buf fer had no significant effect on the concentration dependent relaxatio n in arteries preconstricted with noradrenaline. However, after 2 h pe rfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial functi on. Transmission electron microscopy of arteries perfused with STBM ve sicles confirmed endothelial disruption. Conclusions STBM vesicle perf usion specifically altered the relaxation response of preconstricted m aternal subcutaneous fat arteries to acetylcholine, suggesting an alte ration in endothelial dependent relaxation. Deported microvilli may th erefore be capable of producing endothelial cell damage and endothelia l dysfunction observed in the maternal syndrome of pre-eclampsia.